Ovarian Cancer Clinical Trial
Alpelisib Plus Olaparib in Platinum-resistant/Refractory, High-grade Serous Ovarian Cancer, With no Germline BRCA Mutation Detected
Summary
The objective of this study is to assess the efficacy and safety of the combination of alpelisib and olaparib compared with single agent cytotoxic chemotherapy in patients with platinum resistant or refractory high-grade serous ovarian cancer, with no germline BRCA mutation detected.
Full Description
This study will include adult women with platinum resistant or refractory high-grade serous ovarian cancer, with no germline BRCA mutation detected. Participants will be randomized in a 1:1 ratio to either alpelisib plus olaparib or single agent cytotoxic chemotherapy (paclitaxel or PLD) in this open-label, active controlled study.
Participants will continue to receive study treatment until disease progression, unacceptable toxicity that precludes further treatment, or until discontinuation of study treatment due to any other reason. After treatment discontinuation, all participants will enter in the post-treatment follow-up period, which consists of a safety follow-up visit and a 9-week post-progression visit. Once they complete the post-treatment follow-up, participants will then enter the survival follow-up period.
Eligibility Criteria
Inclusion Criteria:
Participant has histologically confirmed diagnosis of high-grade serous or high-grade endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
Measurable disease, i.e., at least one measurable lesion per RECIST 1.1 criteria (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation)
If no measurable disease is present, the disease should be assessable by Gynecologic Cancer Intergroup criteria (GCIC) for CA-125
Participant has no germline BRCA1/2 mutation as determined by an FDA approved assay.
Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Participant has platinum-resistant (progression within one to six months after completing platinum-based therapy) or platinum refractory disease (progression during treatment or within 4 weeks after the last dose), where platinum-based therapy is not an option, according to the GCIG 5th Ovarian Cancer Consensus Conference definitions. The platinum-based chemotherapy regimen does not necessarily need to be the last regimen the participant received prior to study entry.
Participant must have received at least one but no more than three prior systemic treatment regimens and for whom single-agent chemotherapy is appropriate as the next line of treatment.
Participant has adequate bone marrow and organ function
Exclusion Criteria:
Participant has received prior treatment with any PI3K, mTOR or AKT inhibitor.
Participant is concurrently using other anti-cancer therapy
Participant is in a state of small or large bowel obstruction or has other impairment of gastrointestinal (GI) function or GI disease
Participant has had surgery within 14 days prior to starting study drug or has not recovered from major side effects
Participant has not recovered from all toxicities 5 related to prior anticancer therapies to baseline or NCI CTCAE Version 4.03 Grade ≤1. Exception to this criterion: participants with any grade of alopecia are allowed to enter the study.
Participants with liver impairment and Child Pugh score B or C
Participant has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤2 weeks prior to randomization, and who has not recovered to baseline, grade 1 or better from related side effects of such therapy (with the exception of alopecia).
Participant has a known hypersensitivity to any of the study drugs or excipients
Other inclusion/exclusion criteria may apply
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There are 92 Locations for this study
Phoenix Arizona, 85016, United States
Phoenix Arizona, 85016, United States
Fort Myers Florida, 33901, United States
West Palm Beach Florida, 33401, United States
Silver Spring Maryland, 20904, United States
Boston Massachusetts, 02114, United States
Boston Massachusetts, 02115, United States
New York New York, 10065, United States
Cincinnati Ohio, 45242, United States
Cincinnati Ohio, 45267, United States
Sioux Falls South Dakota, 57106, United States
Nashville Tennessee, 37203, United States
Bedford Texas, 76022, United States
Dallas Texas, 75246, United States
San Antonio Texas, 78217, United States
Tyler Texas, 75702, United States
Caba Buenos Aires, C1056, Argentina
Caba Buenos Aires, C1125, Argentina
Ciudad Autonoma de Bs As Buenos Aires, C1015, Argentina
Buenos Aires , C1012, Argentina
Randwick New South Wales, 2031, Australia
Bedford Park South Australia, 5041, Australia
Shepparton Victoria, 3630, Australia
Innsbruck Tyrol, 6020, Austria
Graz , 8036, Austria
Bruxelles , 1000, Belgium
Leuven , 3000, Belgium
Namur , 5000, Belgium
Belo Horizonte Minas Gerais, 30130, Brazil
Sao Paulo SP, 04014, Brazil
Calgary Alberta, T2N 4, Canada
Vancouver British Columbia, V5Z 4, Canada
London Ontario, N6A 5, Canada
Toronto Ontario, M4N 3, Canada
Chengdu Sichuan, 61004, China
Tianjin Tianjin, 30006, China
Beijing , 10003, China
Jinan , 25001, China
Shanghai , 20003, China
Novy Jicin Czech Republic, 74101, Czechia
Ostrava Poruba , 708 5, Czechia
Praha 2 , 128 5, Czechia
Herlev , 2730, Denmark
Odense C , DK 50, Denmark
Kuopio , FIN-7, Finland
Tampere , FIN-3, Finland
Turku , FIN-2, Finland
Besancon cedex , 25030, France
Lyon , 69373, France
Paris , 75012, France
Pierre Benite , 69495, France
Villejuif Cedex , 94800, France
Mannheim Baden-Wuerttemberg, 68305, Germany
Berlin , 13353, Germany
Dresden , 01307, Germany
Essen , 45136, Germany
Bologna BO, 40138, Italy
Firenze FI, 50134, Italy
Milano MI, 20133, Italy
Milano MI, 20141, Italy
Roma RM, 8-001, Italy
Vicenza VI, 36100, Italy
Napoli , 80131, Italy
Seoul , 03080, Korea, Republic of
Seoul , 03722, Korea, Republic of
Kota Kinabalu Sabah, 88996, Malaysia
Kuching Sarawak, 93586, Malaysia
Kuala Lumpur Wilayah Persekutuan, 50586, Malaysia
Kuala Lumpur , 59100, Malaysia
Monterrey Nuevo Leon, 64460, Mexico
Ciudad de Mexico , 04700, Mexico
Eindhoven , 5623 , Netherlands
Loures , 26745, Portugal
Porto , 4200-, Portugal
Arkhangelsk , 16304, Russian Federation
Singapore , 11922, Singapore
Singapore , 16858, Singapore
Bratislava , 83310, Slovakia
Cordoba Andalucia, 14004, Spain
Barcelona Catalunya, 08035, Spain
Barcelona Catalunya, 08036, Spain
Valencia Comunidad Valenciana, 46010, Spain
Pamplona Navarra, 31008, Spain
Madrid , 28034, Spain
Taichung , 40705, Taiwan
Taipei , 10002, Taiwan
Taipei , 11217, Taiwan
Adana , 01160, Turkey
Ankara , 06100, Turkey
Ankara , 06520, Turkey
Izmir , , Turkey
Glasgow , G12 0, United Kingdom
London , SE1 9, United Kingdom
Manchester , M20 4, United Kingdom
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